Neurons contact each other mostly by synaptic transmission at synapses. Synaptic transmission relies on vesicle exocytosis, i.e., fusion of vesicles with the plasma membrane and release of transmission. To maintain vesicle exocytosis, fused vesicles must be retrieved, or endocytosed, to form new vesicles for the second round of exocytosis. My goal is to improve our understanding on the cellular and molecular mechanisms underlying synaptic vesicle exocytosis and endocytosis, which are the building block for synaptic transmission and thus the signaling process in the neuronal network. My progress from Oct. 1, 2003 to now is listed in the following. First, we have developed a new method to study exocytosis at a calyx-type synapse in the mammalian central nervous system. This ended up a publication in Journal of Neuroscience Method, 2004. Secondly, we found that a clinically used volatile anesthetic, isoflurane, inhibits synaptic transmission by reducing the presynaptic action potential waveform. This finding may advance our understanding on how volatile anesthetics work to achieve its anesthetic action. The finding has been published in Journal of Anesthesiology, 2004. Third, I have provided an undated review on the study of the kinetic of endocytosis, which is critical for nerve terminals to maintain synaptic transmission. The review was published in Trends in Neuroscience, 2004. Fourthly, we have studied the molecular mechanisms underlying synaptic plasticity, particularly short-term synaptic depression. We found a novel mechanism that may underlie short-term synaptic depression. The work is in preparation of submission. Finally, we are in the progress of developing a method to study the molecular mechanisms of endocytosis. The method may shed light on the molecular mechanisms underlying modulation of the kinetics of endocytosis.